BACKGROUND: The periaqueductal gray (PAG) dysfunction was recognized in migraine, and the nonspecific PAG lesions were also observed in episodic migraine (EM) recently. However, the PAG volume change was not totally detected in EM up to now. Herein, the aim of this study was to investigate altered PAG volume in EM patients based on high resolution brain structural image. METHODS: The brain structural images were obtained from 18 normal controls (NC), 18 EM patients and 16 chronic migraine (CM) on 3...

It is known that diabetic (DBT) animals present dysregulation on the serotonergic system in several brain areas associated with anxiety-like responses. The aim of this study was to investigate the involvement of 5-HT1A receptors on dorsal periaqueductal gray (dPAG) in the behavioral response related to panic disorder in type-1 DBT animals. For this, the escape response by electric stimulation (ES) of dPAG in DBT and normoglycemic (NGL) animals was assessed. Both NGL and DBT animals were exposed to an open-field test (OFT) 28 days after DBT confirmation...

Reported results have shown that the pentapeptide opiorphin inhibits oligopeptidases that degrade brain neuropeptides, and has analgesic and antidepressant effects in experimental animals, without either tolerance or dependency after chronic administration. In a previous study we showed that opiorphin has a panicolytic-like effect in the dorsal periaqueductal gray (dPAG) electrical stimulation test (EST), mediated by the μ-opioid receptor (MOR). This study further analyzes the mechanism of opiorphin panicolytic action, using the EST and drug injection inside the dPAG...

Theoretical models have implicated amygdala dysfunction in the development of Disruptive Behavior Disorders (DBDs; Conduct Disorder/Oppositional Defiant Disorder). Amygdala dysfunction impacts valence evaluation/response selection and emotion attention in youth with DBDs, particularly in those with elevated callous-unemotional (CU) traits. However, amygdala responsiveness during social cognition and the responsiveness of the acute threat circuitry (amygdala/periaqueductal gray) in youth with DBDs have been less well-examined, particularly with reference to CU traits...

Recent reports support higher than expected rates of binge alcohol consumption among women and girls. Unfortunately, few studies have assessed the mechanisms underlying this pattern of intake in females. Studies in males suggest that alcohol concentrations relevant to the beginning stages of binge intoxication may selectively target tonic GABAergic inhibition mediated by GABAA receptor subtypes expressing the δ-subunit protein (δ-GABAAR). Indeed, administration of agonists that interact with these δ-GABAAR prior to alcohol access can abolish binge drinking behavior in male mice...

Tolerance to morphine antinociception hinders its long-term use in clinical practice. Interaction between neuron and microglia has been proved to play critical role in the mechanism of morphine tolerance, while CXCL10/CXCR3 signaling has been implicated in neuron-glia signaling and morphine analgesia. This study aims to investigate whether CXCL10/CXCR3 signaling in periaqueductal gray (PAG) contributes to the development of morphine tolerance by modulating neuron-microglia interaction. The results showed that the expressions of CXCR3 and CXCL10 were gradually increased in parallel with repeated morphine administration and activation of microglia...

Several lines of investigations have shown that in some brain areas, in particular, in the midbrain periaqueductal gray matter, rostral ventromedial medulla, central nucleus of amygdala, nucleus raphe magnus, and dorsal hippocampus, microinjections of nonsteroidal anti-inflammatory drugs (NSAIDs) induce antinociception with distinct development of tolerance. The agranular insular cortex (AIC) is a small region of the cerebral cortex located on the lateral area of the rat's cerebral hemisphere that is involved in the perception and response to pain...

Although there is much evidence for a role of GABAB receptors in the pathophysiology of anxiety, the underlying neuronal mechanisms are largely unclear. The GABAB receptor allosteric positive modulator, GS39783, exerts anxiolytic effects without interfering with GABAB-mediated modulation of body temperature, cognitive performance and locomotor activity thus offering advantages over GABAB receptor agonists. However, the precise neural circuits underlying the anxiolytic effects of GS39783 are unknown. The aim of the present study was to identify brain structures and associated neuronal circuits that are modulated by GS39783 under either basal or mild stress conditions...

The involvement of the reticular formation (RF) in the transmission and modulation of nociceptive information has been extensively studied. The brainstem RF contains several areas which are targeted by spinal cord afferents conveying nociceptive input. The arrival of nociceptive input to the RF may trigger alert reactions which generate a protective/defense reaction to pain. RF neurons located at the medulla oblongata and targeted by ascending nociceptive information are also involved in the control of vital functions that can be affected by pain, namely cardiovascular control...

The midbrain periaqueductal gray (PAG) has been implicated in the generation and transmission of a prediction error signal that instructs amygdala-based fear and extinction learning. However, the PAG also plays a key role in the expression of conditioned fear responses. The evidence for a role of the PAG in fear learning and extinction learning has been obtained almost exclusively using PAG-dependent fear responses. It is less clear whether the PAG regulates fear learning when other measures of learned fear are used...

The median raphe region (MRR) is believed to control the fear circuitry indirectly, by influencing the encoding and retrieval of fear memories by amygdala, hippocampus and prefrontal cortex. Here we show that in addition to this established role, MRR stimulation may alone elicit the emergence of remote but not recent fear memories. We substituted electric shocks with optic stimulation of MRR in C57BL/6N male mice in an optogenetic conditioning paradigm and found that stimulations produced agitation, but not fear, during the conditioning trial...

The cerebrospinal fluid (CSF)-contacting nucleus is implicated in the descending inhibitory pathway in pain processing, whereas the cellular and molecular mechanisms underpinning CSF-contacting nucleus regulating pain signals remains largely elusive. ATP is evidenced to inhibit pain transmission at supraspinal level by the mediation of the receptor P2X, wherein its subtype P2X3 is identified as the most potent. Our present experiment investigated the functionality of P2X3 receptors in CSF-contacting nucleus in the formalin-evoked inflammatory pain...

Sudden unexpected death in epilepsy (SUDEP) is a major concern for patients with epilepsy. In most witnessed cases of SUDEP generalized seizures and respiratory failure preceded death, and pre-mortem neuroimaging studies in SUDEP patients observed changes in specific subcortical structures. Our study examined the role of subcortical structures in the DBA/1 mouse model of SUDEP using manganese-enhanced magnetic resonance imaging (MEMRI). These mice exhibit acoustically-evoked generalized seizures leading to seizure-induced respiratory arrest (S-IRA) that results in sudden death unless resuscitation is rapidly instituted...

Emotionally salient situations usually trigger arousal along with autonomic and neuroendocrine reactions. To determine whether the extended amygdala plays a role in sleep-wakefulness regulation, we examined the effects of optogenetic and pharmacogenetic excitation of GABAergic neurons in the bed nucleus of the stria terminalis (GABA(BNST) neurons). Acute optogenetic excitation of these cells during nonrapid eye movement (NREM) sleep resulted in an immediate state transition to wakefulness, whereas stimulation during REM sleep showed no effect on sleep-wakefulness states in male mice...

Functional connectivity (FC) has been used to investigate the pathophysiology of migraine. We aimed to identify atypical FC between the periaqueductal gray (PAG) and other brain areas in rats induced by repeated meningeal nociception. The rat model was established by infusing an inflammatory soup (IS) through supradural catheters in conscious rats. Quiescent and face-grooming behaviors were observed to assess nociceptive behavior. FC analysis seeded on the PAG was performed on rats 21 days after IS infusion...

[Purpose] The aim of the present study is to detail the protocol for a randomised controlled trial (RCT) of neural manual vs. robotic assisted on pain in sensitivity as well as analyse the quantitative and qualitative movement of hand in subjects with hand osteoarthritis. [Subjects and Methods] Seventy-two patients, aged 50 to 90 years old of both genders, with a diagnosis of hand Osteoarthritis (OA), will be recruited. Two groups of 36 participants will receive an experimental intervention (neurodynamic mobilization intervention plus exercise) or a control intervention (robotic assisted passive mobilization plus exercise) for 12 sessions over 4 weeks...

The dorsomedial hypothalamus (DMH) and the dorsal periaqueductal gray (DPAG) have been implicated in the genesis and regulation of panic-related defensive behaviors, such as escape. Previous results point to an interaction between serotonergic and opioidergic systems within the DPAG to inhibit escape, involving µ-opioid and 5-HT1A receptors (5-HT1AR). In the present study we explore this interaction in the DMH, using escape elicited by electrical stimulation of this area as a panic attack index. The obtained results show that intra-DMH administration of the non-selective opioid receptor antagonist naloxone (0...